Monozygotic twins discordant for Huntington disease after 7 years.

BACKGROUND: Huntington disease (HD) has only rarely been identified in identical twins. All described twins have had disease onset within 1 year of each other, suggesting that disease onset is determined solely by genetic influences. OBJECTIVE: To describe a unique set of monozygotic twins in whom clinical HD onset is at least 7 years apart. DESIGN: A 71-year-old woman was diagnosed as having HD based on medical history, physical examination results consistent with HD, and a CAG trinucleotide repeat number of 39 in the HD gene on chromosome 4. Her onset was 6 years earlier. Her genetically confirmed identical twin, carrying the same number of CAG repeats, was neurologically healthy when examined the next year. Only the HD-manifest twin had chronic bronchitis, rheumatoid arthritis, type 2 diabetes mellitus, and chronic anemia. Both had hypertension. CONCLUSIONS: To our knowledge, this is the first report of monozygotic twins discordant for HD by more than 2 years. The onset of HD symptoms in a patient with 39 triplet repeats at least 7 years earlier than her identical twin suggests the possibility that the disease may be initiated (or delayed) by environmental factors. We have identified increased cigarette use and longer exposure to various industrial toxins as potential explanations for the earlier onset in one twin.

Rebound psychosis: effect of discontinuation of antipsychotics in Parkinson's disease.

To determine whether psychiatrically stable patients with a history of drug-induced psychosis could be successfully weaned off their antipsychotic drug, we offered consecutive Parkinson disease (PD) patients on quetiapine or clozapine, who were free of any on-going psychosis, to be slowly weaned off their antipsychotic drug. Before the study was aborted 6 PD patients (mean age, 78 years) with an average antipsychotic exposure of 20 months (5 on quetiapine, 1 on clozapine) were enrolled. After the antipsychotic agent was discontinued, psychosis recurred in 5 of 6 patients. In 3 patients the "rebound psychosis" was worse than the original psychotic episode and required subsequent higher antipsychotic medication doses.

Botulinum toxin type B for gait freezing in Parkinson's disease.

BACKGROUND: Freezing of Gait (FOG) can be a serious problem in Parkinson's disease (PD) and is usually refractory to medical treatment. Botulinum toxin (BTX) type A has been reported to relieve FOG in small open label studies. MATERIAL/METHODS: We performed a double-blind, placebo-controlled, parallel-group study using BTX-B injections on the soleus-gastrocnemius muscle complex of the predominantly affected leg in freezing. Patients were evaluated at baseline and monthly thereafter until endpoint was reached. UPDRS parts II and III, Visual Analog Scale (VAS), Clinical Global Impression Scale (CGIS) and Modified Webster Step-Seconds test were the used to measure efficacy. RESULTS: 14 out of 17 patients screened with idiopathic PD and FOG refractory to medical treatment met inclusion criteria for the study. 9 patients were randomized to 5,000 U of BTX-B treatment and 5 patients to placebo. Our cohort had a mean age of 74 years, and average PD duration of 10 years. Based on the CGIS, 1 patient was much improved, 2 patients had minimal improvement, 9 were unchanged from baseline and 2 were minimally worse. There was no significant difference between the treatment and placebo arms in the number of patients improved versus unchanged. There were no significant differences between the treatment and placebo arms in the UPDRS II and III, VAS, or Modified Webster Step-Seconds scores between the treatment and placebo arms, at baseline and after treatment. CONCLUSIONS: 5,000 U of BTX-B injected in one leg did not significantly improve FOG. However, since the power of the study was low, a small beneficial effect may have been missed.

Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience.

Aripiprazole is the newest atypical antipsychotic (AA) drug to be released in the US. It is the only AA that is a partial agonist at the D2 and 5HT1a receptors and an antagonist at 5HT2a receptors. It also has a high 5HT2/D2 ratio and may therefore carry a low risk of extrapyramidal side effects and alleviate psychosis in Parkinson-vulnerable populations. We report our preliminary experience in 8 patients with probable Parkinson disease (PD) treated with aripiprazole for drug-induced psychosis. Two patients were neuroleptic-naive, 5 patients were "quetiapine failures", and 1 patient was switched from olanzapine to aripiprazole. Aripiprazole was started at 5 mg to 10 mg a day and slowly increased over 3 to 7 days until side effects or improvement of psychosis occurred. Only 2 out of 8 patients experienced near complete resolution of their psychosis using aripiprazole. The other six patients discontinued aripiprazole within 40 days, 2 of whom discontinued due to motor worsening. Our preliminary experience with aripiprazole is mixed but not very encouraging. Controlled studies are needed to evaluate aripiprazole in parkinsonian patients.

Treatment of psychosis in Parkinson's disease: safety considerations.

Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much more commonly, psychosis is induced by drug therapy for Parkinson's disease and is the strongest known risk factor for nursing home placement. Delusions are less frequent than hallucinations, but are more concerning as they are often paranoid in nature. Treatment begins with a search for correctable infectious, toxic, and metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications are slowly reduced. However, withdrawal of these drugs usually worsens parkinsonism and is often not tolerated. Certain atypical antipsychotics can be used to treat psychosis without compromising motor function. The choice of atypical antipsychotic is largely based on ease of use and adverse effect profile as most have comparable efficacy in improving psychosis. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not been reported in Parkinson's disease. The most common adverse effects of clozapine in Parkinson's disease are sedation, orthostatic hypotension and sialorrhoea. Sedation is generally helpful since these patients are frequently awake at night and tend to have worse behavioural problems then. Clozapine does not induce deterioration of motor function, but it has the potential to cause agranulocytosis, which is idiosyncratic and not dose-related. In risperidone-treated Parkinson's disease patients, reported adverse effects include somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium, fatigue, leg cramps, depression, urinary incontinence and hypotension. Although in some Parkinson's disease studies, risperidone has been well tolerated, others have shown that many patients are unable to tolerate the drug due to deterioration of motor function. While an initial study of olanzapine in Parkinson's disease psychosis showed the drug to be effective without deterioration of motor function, succeeding reports demonstrated a deleterious effect of the drug on motor functioning. The most common adverse effects of quetiapine in Parkinson's disease patients are sedation and orthostatic hypotension. There is a lack of double-blind trials; however, cumulative reports involving >200 Parkinson's disease patients strongly suggest that quetiapine is well tolerated and effective. Unlike clozapine, it does not improve tremor and may induce mild deterioration of motor function. Recently, cholinesterase inhibitors have been reported to alleviate psychosis in Parkinson's disease. Although ondansetron, an antiemetic with antiserotonergic properties, has been reported to relieve psychosis in Parkinson's disease, its prohibitive cost has prevented further study in this population. Electroconvulsive treatment is generally reserved for the patient with psychotic depression who is unable to tolerate any pharmacological therapy.

Long-term outcome of quetiapine use for psychosis among Parkinsonian patients.

To evaluate the long-term efficacy and tolerability of quetiapine for psychosis among parkinsonian patients, a retrospective analysis of all parkinsonian patients taking quetiapine for psychosis in a single movement disorders center was carried out. Demographic data, including type and severity of psychosis, presence of dementia, treatment response, before and after Unified Parkinson's Disease Rating Scale (UPDRS)-motor scores and Hoehn and Yahr (H&Y) scale were obtained. One hundred six parkinsonian patients with a mean age of 76.6 years were on an average levodopa (L-dopa) dose of 415 mg/d. Seventy-eight of 106 (74%) remained on quetiapine for a mean duration of 15 months at an average dose of 60 mg per day. Eighty-seven (82%) patients had partial or complete resolution of their psychosis whereas 19 (18%) patients had no improvement on quetiapine. Motor worsening was noted in 34 (32%) patients but was uncommonly sufficient to warrant quetiapine discontinuation. More quetiapine non-responders were noted to be demented, delusional, and experienced threatening psychosis but only the presence of dementia remained significant on multivariate analysis (OR = 11.6; 95% CI = 1.4-92.9). Also, patients who developed motor worsening while on quetiapine tended to be more demented (P = 0.07).

Quetiapine for psychosis in Parkinson's disease versus dementia with Lewy bodies.

BACKGROUND: Most clinicians perceive psychosis in dementia with Lewy bodies (DLB) as more difficult to treat than Parkinson's disease, yet there are no reports comparing the antipsychotic response between the 2 disorders. METHOD: All charts of Parkinson's disease and DLB patients at our Movement Disorders Center, Memorial Hospital of Rhode Island, Pawtucket, given quetiapine for psychosis were reviewed. Demographic data, including type and severity of psychosis, before and after Unified Parkinson's Disease Rating Scale (UPDRS)-motor scores, motor worsening, and treatment response (recorded as poor/none, partial, or total), were obtained. The chi-square test was used to assess differences in efficacy and tolerability of quetiapine between Parkinson's disease and DLB patients. RESULTS: Eighty-seven Parkinson's disease and 11 DLB patients with psychosis were analyzed. No significant difference in mean age, levodopa dose, quetiapine dose, duration of quetiapine use, or baseline UPDRS-motor score was noted between Parkinson's disease and DLB patients. Eighty percent (70/87) of Parkinson's disease patients and 90% (10/11) of DLB patients had partial to complete resolution of psychosis using quetiapine (p = .40). Motor worsening was noted at one point in 32% (28/87) of Parkinson's disease and 27% (3/11) of DLB patients over the duration of quetiapine use (p = .74). CONCLUSION: Long-term quetiapine use was generally well tolerated in this geriatric Parkinson's disease and DLB population. Mild motor worsening occurred in some patients. No significant difference in long-term efficacy and motor worsening associated with quetiapine treatment was noted between the 2 disorders.